Characterization of gene expression changes induced by liver FGFR4 silencing in mice on HFD. Principal component analysis (PCA) (A) and volcano plot (B) of liver RNA-sequencing data from mice on HFD receiving either the saline solution or the siRNA targeting FGFR4. Most significant pathway upregulated (C) and downregulated (D) by liver FGFR4 silencing in HFD mice. Principal component analysis (PCA) (E) and volcano plot (F) of ileum RNA-sequencing data from mice on HFD receiving either the saline solution or the siRNA targeting FGFR4. G: Measure of fgf15 and Shp gene expression in ileal biopsies from mice on HFD. Data are expressed as mean ± SEM and were normalized by the control condition in chow diet mice (n = 4, ns = non-significant, ∗ P < 0.05; ∗∗∗ P < 0.001, moderated t test). H: Most significant pathway downregulated by liver FGFR4 silencing in the ileum of HFD mice. FGFR, fibroblast growth factor receptor; HFD, high-fat diet.